This study is a prospective investigation comparing the efficacy and safety of Janus kinase inhibitors versus calcineurin inhibitors as initial therapy for interstitial lung disease associated with antisynthetase syndrome. The goal is to determine which treatment is more effective at improving lung function and preventing disease progression, while comparing their safety profiles. The findings will help provide clearer treatment guidance for doctors and patients.
Age 18 to 75 years.
Meet the 2017 EULAR/ACR diagnostic criteria for Anti-synthetase Syndrome (ASS).
Presence of Interstitial Lung Disease (ILD) confirmed by High-Resolution Computed Tomography (HRCT).
Active disease requiring initiation or intensification of immunosuppressive therapy, with no prior use of glucocorticoids, immunosuppressants, or biologics.
Diagnosis of Rapidly Progressive ILD (RP-ILD), defined as worsening dyspnea within 1 month and PaO2/FiO2 ratio < 250 mmHg.
Active uncontrolled severe infection, malignancy, or major organ failure.
Pregnancy or lactation.
Contraindications to the study drugs.
Parallel
JAK Inhibitor
DrugOral JAK inhibitors (tofacitinib 5 mg twice daily, or baricitinib 4 mg once daily, or upadacitinib 15 mg once daily) administered in combination with standard glucocorticoid therapy for 12 months.
Calcineurin Inhibitors (CNI)
DrugOral calcineurin inhibitors (tacrolimus 0.075 mg/kg/day in two divided doses, or cyclosporine 2-5 mg/kg/day in two divided doses) administered in combination with standard glucocorticoid therapy for 12 months.
12-month survival rate
Proportion of participants surviving at 12 months after randomization, with survival defined as the time from randomization to death from any cause.
Annual decline rate of lung function (FVC% and DLCO%)
The annual rate of decline in forced vital capacity (FVC% predicted) and diffusing capacity for carbon monoxide (DLCO% predicted), calculated as the change from baseline to 12 months.
Change in HRCT score
Change in high-resolution computed tomography (HRCT) score from baseline to 12 months, assessed using a standardized scoring system.
Rate of glucocorticoid tapering
The rate of glucocorticoid dose reduction over 12 months, calculated as the time to achieve prednisone ≤7.5 mg/day or the cumulative glucocorticoid dose.
Proportion of patients achieving low disease activity (LDA)
Proportion of participants achieving low disease activity (LDA) at 6 and 12 months, defined as meeting all of the following criteria: no active arthritis without regular NSAID use; no active myositis with serum creatine kinase ≤ upper limit of normal; stable ILD with no decline in pulmonary function (FVC decline \<5% and DLCO decline \<10% in the past 6 months); no fever or other systemic manifestations with ESR \<20 mm/h; stable glucocorticoid dose ≤7.5 mg/day (prednisone equivalent) for at least 3 months.
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